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How is acute lymphocytic leukemia diagnosed?

Certain signs and symptoms can suggest that a person might have acute lymphocytic leukemia, but tests are needed to confirm the diagnosis.

Medical history and physical exam

If you have signs and symptoms that suggest you might have leukemia, the doctor will want to get a thorough medical history, including how long you have had symptoms and if you have any history of exposure to risk factors.

During the physical exam, the doctor will probably focus on any enlarged lymph nodes, areas of bleeding or bruising, or possible signs of infection. The eyes, mouth, and skin will be looked at carefully, and a thorough nervous system exam may be done. Your abdomen will be felt for signs of an enlarged spleen or liver.

Your doctor may also order tests of your blood cell counts. If the results suggest leukemia, the doctor may refer you to a hematologist, a doctor who specializes in treating blood disorders (including blood cancers like leukemia). This doctor may run one or more of the tests described below.

Tests used to diagnose and classify ALL

If your doctor thinks you have leukemia, he or she will need to check samples of cells from your blood and bone marrow to be sure of the diagnosis. Other tissue and cell samples may also be taken to help guide treatment.

Blood tests

Blood samples for ALL tests are generally taken from a vein in the arm.

Complete blood count (CBC) and blood cell exam (peripheral blood smear): The complete blood count (CBC) measures the numbers of red blood cells, white blood cells, and platelets. This test is often done along with a differential (or diff) which looks at the numbers of the different types of white blood cells. These tests are often the first ones done on patients with a suspected blood problem.

For the peripheral blood smear (sometimes just called a smear), a drop of blood is smeared across a slide and then looked at under a microscope to see how the cells look. Changes in the numbers and the appearance of the cells often help diagnose leukemia.

Most patients with ALL have too many immature white cells in their blood, and not enough red blood cells or platelets. Many of the white blood cells will be lymphoblasts (blasts), which are immature lymphocytes not normally found in the bloodstream. Lymphoblasts do not function like normal, mature white blood cells.

Even though these findings may suggest leukemia, the disease usually is not diagnosed without looking at a sample of bone marrow cells.

Blood chemistry and coagulation tests: Blood chemistry tests measure the amounts of certain chemicals in the blood, but they are not used to diagnose leukemia. In patients already known to have ALL, these tests can help detect liver or kidney problems caused by spreading leukemia cells or the side effects of certain chemotherapy drugs. These tests also help determine if treatment is needed to correct low or high blood levels of certain minerals.

Blood coagulation tests may also be done to make sure the blood is clotting properly.

Bone marrow tests

Bone marrow aspiration and biopsy: Bone marrow samples are obtained by bone marrow aspiration and biopsy – tests usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases they may be taken from the sternum (breastbone) or other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the skin and the surface of the bone by injecting a local anesthetic, which may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most patients still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is twisted as it is pushed down into the bone. With local anesthetic, most patients just feel some pressure and tugging from the biopsy, but a few may feel a brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.

These bone marrow tests are used to help diagnose leukemia. They may also be done again later to tell if the leukemia is responding to treatment.

Routine exams under a microscope: The bone marrow is looked at under a microscope by a pathologist (a doctor specializing in lab tests) and may be reviewed by the patient’s hematologist/oncologist (a doctor specializing in cancer and blood diseases).

The doctors will look at the size, shape, and other traits of the white blood cells in the samples to classify them into specific types.

A key factor is whether the cells appear mature (look like normal blood cells), or immature (lacking features of normal blood cells). The most immature cells are called lymphoblasts (or blasts for short).

Determining what percentage of cells in the bone marrow are blasts is particularly important. A diagnosis of ALL generally requires that at least 20% to 30% of the cells in the bone marrow are blasts. Under normal circumstances, blasts are never more than 5% of bone marrow cells.

Sometimes just counting and looking at the cells doesn’t provide a definite diagnosis, and other lab tests are needed.

Cytochemistry: In cytochemistry tests, cells are put on a slide and exposed to chemical stains (dyes) that react only with certain substances found in or on different kinds of cells. These stains cause color changes that can be seen under a microscope, which can help the doctor determine what types of cells are present. For instance, one stain will turn parts of acute myeloid leukemia (AML) cells black, but has no effect on ALL cells.

Flow cytometry and immunohistochemistry: These tests are used for immunophenotyping – classifying cells according to proteins on or in the cells. This kind of testing is very helpful in determining the exact type of leukemia present. For diagnosing leukemia, it is most often done on cells from bone marrow, but it can also be done on cells from the blood, lymph nodes, and other body fluids.

For both flow cytometry and immunohistochemistry, samples of cells are treated with antibodies that stick to certain proteins. For immunohistochemistry, the cells are examined under a microscope to see if the antibodies stuck to them and so they have those proteins, while for flow cytometry a special machine is used.

These tests are helpful in diagnosing leukemia and lymphoma. For ALL, they are most often used to help determine the exact subtype of ALL in someone already thought to have the disease based on looking at the blood and bone marrow under a microscope.

Chromosome testing

Normal human cells contain 23 pairs of chromosomes (bundles of DNA). In some cases of leukemia, the cells have chromosome changes. Sometimes a piece of a chromosome is missing – called a deletion.

More often in ALL, 2 chromosomes swap some of their DNA, so that part of one chromosome becomes attached to part of a different chromosome. This is called a translocation. The most common chromosome change in adult ALL is a translocation between chromosomes 9 and 22 [often written t(9;22)], which results in a shortened chromosome 22 (called the Philadelphia chromosome). About 1 out of 4 adults with ALL have this abnormality in their leukemia cells. This change is especially important because it can be targeted with certain drugs.

Information chromosome changes can be useful in predicting a person’s outlook and response to treatment. For this reason, chromosome testing is a standard part of the work-up of ALL patients.

Cytogenetics: For this test, the cells are grown in lab dishes until they start dividing and the chromosomes can be seen under a microscope. Then the chromosomes are looked at under a microscope to detect any changes.

Because it takes time for the cells to start dividing, cytogenetic testing often takes about 2 to 3 weeks. It is often used to look at cells in the bone marrow, but it can also be used to look at cells from the blood. An advantage of cytogenetic testing is that it looks at all of the chromosomes, and the doctor doesn’t have to know in advance what changes to test for.

Not all chromosome changes can be seen under a microscope. Other lab tests can often help find these changes.

Fluorescent in situ hybridization (FISH): This is another way to look at chromosomes and genes. It uses special fluorescent dyes that only attach to specific genes or parts of particular chromosomes. FISH can find most chromosome changes (such as translocations) that are visible under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.

FISH can be used on regular blood or bone marrow samples. Because the cells don’t have to be able to divide for this test, tt can also be used to look at cells from other tissues, like lymph node samples. It is very accurate and can usually provide results within a couple of days. But because FISH only tests for certain gene changes (and doesn’t look at the chromosomes overall), it is best for looking for the changes that are important based on the kind of leukemia a person has.

Polymerase chain reaction (PCR): This is a very sensitive DNA test that can also find certain gene changes too small to be seen with a microscope, even if very few leukemia cells are present in a sample. Like FISH, it is used to find particular gene changes and not to look at the chromosomes overall. For ALL, it is often used to look for the gene made by the Philadelphia chromosome.

If the leukemia cells have a particular gene (or chromosome) change, PCR can be used after treatment to try to find small numbers of leukemia cells that may not be visible with a microscope.

Lumbar puncture (spinal tap)

ALL can spread to the area around the brain and spinal cord. To check for this spread, doctors remove a sample of the fluid from that area (cerebrospinal fluid or CSF) for testing.

You may lay on your side or sit up for this test. The doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then placed between the bones of the spine and into the area around the spinal cord to collect some fluid.

A lumbar puncture can also be used to put chemotherapy drugs into the CSF to try to prevent or treat the spread of leukemia to the spinal cord and brain.

Lymph node biopsy

Removing a lymph node or part of a lymph node is often done to help diagnose lymphomas, but is only rarely needed with leukemia because the diagnosis is usually made looking at blood and bone marrow.

In this procedure, a surgeon cuts through the skin to remove all or part of a lymph node. If the node is near the skin surface, this is a simple operation that can often be done with local anesthesia, but if the node is inside the chest or abdomen, general anesthesia is used to keep you asleep during the biopsy.

When the entire lymph node is removed, it is called an excisional lymph node biopsy. If only part of the lymph node is removed, it is called an incisional lymph node biopsy.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce pictures of the inside of the body. Because leukemia does not usually form tumors, imaging tests aren’t as useful as they are for other types of cancer.

Imaging tests might be done in people with ALL, but they are done more often to look for infections or other problems, rather than for the leukemia itself. In some cases they may be done to help determine the extent of the disease, if it is thought it may have spread beyond the bone marrow and blood.

X-rays

Chest x-rays may be done if the doctor suspects a lung infection. They may also be done to look for enlarged lymph nodes in the chest.

Computed tomography (CT) scan

The CT scan is a type of x-ray test that produces detailed, cross-sectional images of your body. Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs).

This test can help tell if any lymph nodes or organs in your body are enlarged. It isn’t usually needed to diagnose ALL, but it may be done if your doctor suspects leukemia cells are growing in an organ, like your spleen.

Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into detailed images of the part of your body being studied.

Before the scan, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body. You may need an IV line for injecting the contrast dye. The IV injection of contrast dye can cause a feeling of flushing or warmth in the face or elsewhere. Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies or have ever had a reaction to any contrast material used for x-rays.

A CT scanner has been described as a large donut, with a narrow table in the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken.

In some cases, a CT can be used to guide a biopsy needle precisely into a suspected abnormality, such as an abscess. For this procedure, called a CT-guided needle biopsy, you stay on the CT scanning table while a radiologist moves a biopsy needle through the skin and toward the mass. CT scans are repeated until the needle is within the mass. A biopsy sample is then removed to be looked at under a microscope.

Sometimes a test that combines the CT scan with a PET (positron emission tomography) scan (PET/CT scan) is done. For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. The amount of radioactivity used is low. Because cancer cells in the body grow rapidly, they absorb large amounts of the sugar. A special camera can then create a picture of areas of radioactivity in the body. The PET/CT scan lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT. This is not often needed for patients with ALL.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the body and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details. This contrast material is different from the one used for CT scans.

MRI scans are very helpful in looking at the brain and spinal cord.

MRI scans take longer than CT scans − often up to an hour. You may have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that you may find disturbing. Some places provide headphones or earplugs to help block this noise out.

Ultrasound

Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. Usually for this test, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with gel). The transducer emits sound waves and picks up the echoes as they bounce off the organs. A computer converts the echoes into an image that is displayed on a computer screen.

Ultrasound can be used to look at lymph nodes near the surface of the body or to look for enlarged organs inside your abdomen such as the kidneys, liver, and spleen.

This is an easy test to have, and it uses no radiation. For most ultrasounds, you simply lie on a table, and a technician moves the transducer over the part of your body being looked at.

Gallium scan and bone scan

These tests are not often done for ALL, but they may be useful if you have bone pain that might be caused by either an infection or cancer in the bones.

For these tests, the doctor or nurse injects a slightly radioactive chemical into the bloodstream. The chemical collects in areas of cancer or infection, which can then be seen with a special type of camera. The images from these scans are seen as “hot spots” in the body, but they don’t provide much detail. If an area lights up on the scan, other imaging tests such as x-rays, CTs, or MRIs may be done to get a more detailed look at the area. If leukemia is a possibility, a biopsy of the area may be needed to confirm this.